The Src family of nonreceptor tyrosine kinases regulates numerous cellular processes, including proliferation, differentiation, migration, survival and angiogenesis. In solid tumors, Src is frequently aberrantly active, and promotes tumor progression and metastasis[3]. Six of Src family kinases (Fyn, Lyn, Fgr, Hck, Src and Yes), are present in megakaryocytes (Mks). Src kinases are negative factors of megakaryocytopoiesis induced by thrombopoietin. The inhibitors of Src kinases might be useful as agents inducing maturation of Mks[4]. Src is highly expressed in CNS neurons and contributes not only to developmental proliferation and differentiation but also to high-order brain functions, such as those contributing to alcohol consumption. Src knock-out mice exhibit no CNS abnormalities, presumably due to compensation by other Src family kinases (SFKs), but have a shortened lifespan and osteopetrosis-associated defects, impeding investigations of the role of Src on behavior in adult mice[5]. Src-I1, is found to be a potent inhibitor of Src (IC50=0.18 μM), but also inhibited other Src family members, such as Lck, Csk and Yes with similar potency to Src, and RIP2 (IC50=0.026 μM) with even greater potency. In addition, it inhibited CHK2 with similar potency to Src, and Aurora B with slightly lower potency[6]. Src-I1 is competitive with both ATP and peptide binding sites of the kinase. The IC50 values are 44 and 88 nM for Src and Lck, respectively[7].
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